Study Questions:

What are the prevalence and predictors of influenza vaccination among participants in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, and what are associations between receiving influenza vaccine and mortality and adverse outcomes?

Methods:

This was a post hoc analysis of the PARADIGM-HF trial, in which patients with heart failure were randomized to the angiotensin receptor neprilysin inhibitor LCZ696 (sacubitril/valsartan) or enalapril. Participants in the trial were asked if they received the seasonal influenza vaccine during the previous 12 months. Cox-proportional hazard models were constructed to investigate associations of influenza vaccination with the risk for all-cause mortality, cardiovascular death or heart failure hospitalization, all-cause hospitalizations, and cardiopulmonary or influenza-related hospitalizations, in adjusted as well as propensity-matched models.

Results:

Of 8,399 participants in the PARADIGM-HF trial, 1,769 (21%) received influenza vaccination within a 12-month period while enrolled in the study. Top predictors of vaccination included enrolling country, white race, implanted defibrillator, older age, lower New York Heart Association functional class, lower heart rate, and a history of diabetes mellitus. Highest vaccination rates were observed in the Netherlands (77.5%), Great Britain (77.2%), and Belgium (67.5%); intermediate rates in North America (52.8%); and lowest rates in Asia (2.6%). Influenza vaccination was associated with a reduced risk for all-cause mortality in propensity-adjusted (hazard ratio, 0.81; 95% confidence interval, 0.67-0.97; p = 0.015) models. Vaccination was associated with increased rates of cardiopulmonary, influenza-related, and all-cause hospitalization in unadjusted models, but not in propensity-adjusted models.

Conclusions:

In a cohort of patients with heart failure with reduced ejection fraction and well managed on optimal medical therapy, there was significant regional variation in influenza vaccination, and such vaccination was associated with reduced all-cause mortality in propensity-adjusted models.

Perspective:

This is an important study that draws attention to the underutilization of influenza vaccination in many regions of the world, including North America. While the reasons for such underuse are clearly multifactorial, current guidelines suggest annual influenza vaccination in patients with heart failure. Findings from this post hoc analysis of the PARADIGM-HF trial would only bolster such recommendations by establishing an association between self-reported influenza vaccination and all-cause mortality.